Brain Communications,
Год журнала:
2024,
Номер
6(2)
Опубликована: Янв. 1, 2024
Abstract
To
explore
the
causal
relationship
between
age
and
brain
health
(cortical
atrophy,
white
matter
integrity,
hyperintensities
cerebral
microbleeds
in
various
regions)
related
multiparameter
imaging
features
using
two-sample
Mendelian
randomization.
Age
was
determined
as
chronological
of
subject.
Cortical
volume,
micro-integrity,
hyperintensity
volume
each
region
were
included
phenotypes
for
health.
genetic
data
analysed
to
determine
inverse-variance
weighted
model,
validated
by
heterogeneity
horizontal
pleiotropy
variables.
is
causally
increased
volumes
(β
=
0.151).
For
fibres
inferior
cerebellar
peduncle
(axial
diffusivity
β
−0.128,
orientation
dispersion
index
0.173),
−0.136),
superior
fronto-occipital
fasciculus
(isotropic
fraction
0.163)
within
limbic
system
deteriorated.
We
also
detected
decreased
cortical
thickness
multiple
frontal
temporal
regions
(P
<
0.05).
Microbleeds
not
with
aging
>
Aging
a
threat
health,
leading
atrophy
mainly
lobes,
well
degeneration
especially
abnormal
deteriorated
integrity
around
hippocampus.
Phase
separation,
a
biophysical
segregation
of
subcellular
milieus
referred
as
condensates,
is
known
to
regulate
transcription,
but
its
impacts
on
physiological
processes
are
less
clear.
Here,
we
demonstrate
the
formation
liquid-like
nuclear
condensates
by
SGF29,
component
SAGA
transcriptional
coactivator
complex,
during
cellular
senescence
in
human
mesenchymal
progenitor
cells
(hMPCs)
and
fibroblasts.
The
Arg
207
within
intrinsically
disordered
region
identified
key
amino
acid
residue
for
SGF29
form
phase
separation.
Through
epigenomic
transcriptomic
analysis,
our
data
indicated
that
both
condensate
H3K4me3
binding
essential
establishing
precise
chromatin
location,
recruiting
factors
co-activators
target
specific
genomic
loci,
initiating
expression
genes
associated
with
senescence,
such
CDKN1A.
alone,
however,
may
not
be
sufficient
drive
or
achieve
transactivation
functions.
Our
study
establishes
link
between
separation
aging
regulation,
highlighting
functional
unit
facilitate
shaping
landscapes
aging.
Protein & Cell,
Год журнала:
2024,
Номер
15(8), С. 612 - 632
Опубликована: Апрель 5, 2024
Abstract
Aging
has
a
profound
impact
on
the
gingiva
and
significantly
increases
its
susceptibility
to
periodontitis,
worldwide
prevalent
inflammatory
disease.
However,
systematic
characterization
comprehensive
understanding
of
regulatory
mechanism
underlying
gingival
aging
is
still
lacking.
Here,
we
systematically
dissected
phenotypic
characteristics
during
in
primates
constructed
first
single-nucleus
transcriptomic
landscape
aging,
by
which
panel
cell
type-specific
signatures
were
elucidated.
Epithelial
cells
identified
as
most
affected
types
gingiva.
Further
analyses
pinpointed
crucial
role
YAP
epithelial
self-renew
homeostasis,
declined
cells,
especially
basal
cells.
The
decline
activity
was
confirmed
human
tissues,
downregulation
primary
keratinocytes
recapitulated
major
defects
observed
aged
primate
while
overexpression
showed
rejuvenation
effects.
Our
work
provides
an
in-depth
serves
rich
resource
for
developing
novel
strategies
combat
aging-associated
diseases,
with
ultimate
goal
advancing
periodontal
health
promoting
healthy
aging.
Abstract
Reactivation
of
retroelements
in
the
human
genome
has
been
linked
to
aging.
However,
whether
epigenetic
state
specific
can
predict
chronological
age
remains
unknown.
We
provide
evidence
that
locus‐specific
retroelement
DNA
methylation
be
used
create
retroelement‐based
clocks
accurately
measure
immune
system,
across
tissues,
and
pan‐mammalian
species.
also
developed
a
highly
accurate
clock
compatible
with
EPICv.2.0
data
was
constructed
from
CpGs
did
not
overlap
existing
first‐
second‐generation
clocks,
suggesting
unique
signal
for
previously
captured.
found
were
reversed
during
transient
reprogramming,
accelerated
people
living
HIV‐1,
responsive
antiretroviral
therapy.
Our
findings
highlight
utility
biomarkers
aging
support
renewed
emphasis
on
role
geroscience.
Abstract
Aging
is
an
intricate
process
involving
interactions
among
multiple
factors,
which
one
of
the
main
risks
for
chronic
diseases,
including
Alzheimer's
disease
(AD).
As
a
member
cysteine
protease,
cathepsin
S
(CTSS)
has
been
implicated
in
inflammation
across
various
diseases.
Here,
we
investigated
role
neuronal
CTSS
aging
and
AD
started
by
examining
expression
hippocampus
neurons
mice
identified
significant
increase,
was
negatively
correlated
with
recognition
abilities.
Concurrently,
observed
elevation
concentration
serum
elderly
people.
Transcriptome
fluorescence‐activated
cell
sorting
(FACS)
results
revealed
that
overexpression
aggravated
brain
inflammatory
milieu
microglia
activation
to
M1
pro‐inflammatory
phenotype,
chemokine
C‐X3‐C‐motif
ligand
1
(CX3CL1)—chemokine
receptor
(CX3CR1)
axis
janus
kinase
2
(JAK2)—signal
transducer
activator
transcription
3
(STAT3)
pathway.
CX3CL1
secreted
acts
on
CX3CR1
microglia,
our
first
time
neuron
neuron–microglia
“crosstalk.”
Besides,
elevated
regions
patients,
hippocampus.
Utilizing
selective
inhibitor,
LY3000328,
rescued
AD‐related
pathological
features
APP/PS1
mice.
We
further
noticed
increased
B
(CTSB)
activity,
but
decreased
L
(CTSL)
activity
microglia.
Overall,
provide
evidence
can
be
used
as
biomarker
plays
regulatory
roles
through
modulating
neuroinflammation
process.
